Cesium carbonate → ethyl 3-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]benzoate

HRID 1691730Notes

Reaction equation

HRID 1691730 reaction equation
O1CCOCC1.[C:7]([O:11][C:12](=[O:39])[N:13]([C@@H:27]([C:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31][CH:30]=1)[CH3:28])[CH2:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH:16]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([CH3:10])([CH3:9])[CH3:8].I[C:41]1[CH:42]=[C:43]([CH:49]=[CH:50][CH:51]=1)[C:44]([O:46][CH2:47][CH3:48])=[O:45].C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.C(OCC)(=O)C.C(O)(C)(C)C>[C:7]([O:11][C:12]([N:13]([CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:41]2[CH:42]=[C:43]([CH:49]=[CH:50][CH:51]=2)[C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:17][CH:16]1[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C@@H:27]([C:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31][CH:30]=1)[CH3:28])=[O:39])([CH3:8])([CH3:9])[CH3:10]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-Dioxane2×HCID 143542Ethyl 3-iodobenzoateHCID 59178521HCID 59178521, compound

Product 1

HCID 66906240ethyl 3-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]benzoateYield 81%

Reagents, catalysts & solvents 4

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 2.3 mg of tris(dibenzylideneacetone)dipalladium(0), 1.9 mg of 2-(dicyclohexylphosphino)-2′-(dimethylamino)biphenyl, and 0.5 mL of 1,4-dioxane were added 100 mg of tert-butyl[(1R)-1-(1-naphthyl)ethyl][(3-phenylpiperidin-4-yl)methyl]carbamate, 83.8 mg of ethyl 3-iodobenzoate, 105 mg of cesium carbonate, 1.0 mL of 1,4-dioxane, and 1.5 mL of t-butanol, followed by stirring at 100° C. overnight. After cooling to room temperature, to the reaction mixture was added ethyl acetate, the insolubles were removed, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 108 mg of ethyl 3-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]benzoate as a pale yellow foamy substance. ESI+: 593

Workup

  1. temperatureAfter cooling to room temperature, to the reaction mixture
  2. customthe insolubles were removed
  3. customthe solvent was removed by distillation under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-73d9afbf22ea4b9b8363dc939f337a8d
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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